Pain management has always been a challenging issue, which is why it has been a major focus of many rigorous studies. Chronic pain which typically lasts for more than three months is prevalent at an astounding rate of 11% to 19% of the adult population. Pain management techniques have gone through major advances in the last decade with no major improvement in the quality of life in affected populations. Recently there has been growing interest in the utilization of stem cells for pain management. Advancement of stem cell therapy has been noted for the past few years and is now being used in human clinical trials. Stem cell therapy has shown promising results in the management of neuropathic, discogenic back, osteoarthritis, and musculoskeletal pain. In this article, we will discuss the role of stem cells in the pain management of the aforementioned conditions, along with the mechanism, adverse effects, and risks of stem cell therapy.

Stem Cell Therapy and Its Significance in Pain Management

Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Much progress has been made in regenerative medicine for the symptomatic treatment of KOA, including products containing stromal vascular fraction (SVF) and platelet-rich plasma (PRP). The aim of this study was to evaluate clinical and radiological findings after the application of autologous conditioned adipose tissue (ACA) and leukocyte-poor PRP (LP-PRP) in patients with mild to moderate KOA. A total of 16 patients (eight male and eight female) with changes related to KOA on the magnetic resonance imaging (MRI), but without severe osteophytosis, full-thickness cartilage loss, or subchondral bone involvement were included in this study. Patients received an intraarticular, ultrasound-guided injection of ACA and LP-PRP. Clinical scores, including a visual analog scale for pain (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated at baseline and at the three and six month follow-ups showing a statistically significant improvements at three and six months post-intervention. Furthermore, the delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) indices were evaluated at baseline and at the three and six month follow-ups showing no significant changes after treatment with ACA and LP-PRP, which were actually equal to the dGEMRIC indices measured in the control group (hyaluronic acid applied in contralateral knees without osteoarthritis). ACA with LP-PRP presents a viable minimally invasive therapeutic option for the clinical improvement of mild to moderate KOA. However, MFAT produced by different systems is likely to differ in cellular content, which can directly affect the paracrine effect (cytokine secretion) of mesenchymal stem cells and consequently the regeneration process.

/pdf/results-of-treating-mild-to-moderate-knee-osteoarthritis-1tv9awg8.pdf

Results of Treating Mild to Moderate Knee Osteoarthritis with Autologous Conditioned Adipose Tissue and Leukocyte-Poor Platelet-Rich Plasma

Osteoarthritis (OA), a principal and challenging disorder of articular cartilage, has been regarded as the most frequent and prevalent chronic disease of degenerative joints, which is caused by multiple factors including aging, trauma, overweight, joint deformity and congenital abnormality, together with the increase in life expectancy. In spite of considerable improvements that have been obtained by conducting multidisciplinary therapies such as surgical procedures and anti-inflammatory drugs, the pathogenesis and efficacy of OA with functional losses and degeneration are still elusively complicated for ascertainment. Mesenchymal stem/stromal cells (MSCs), also termed as multipotent mesenchymal progenitor/precursor cells, skeletal stem cells, or medicinal signaling cells, are heterogeneous cell populations with hematopoietic-supporting and immunomodulatory properties, together with multilineage differentiation property. For decades, investigators have illuminated the application of the advantaged and promising sources with/without remarkable biomaterials for the treatment of recurrent and refractory disorders including OA. In this chapter, we mainly concentrate on the current progress of MSC-based cytotherapy in both preclinical study and clinical practice as well as the promising prospective and critical challenges in the field, which will conformably benefit the administration of OA in future. 

/pdf/mesenchymal-stem-cell-based-cytotherapy-for-osteoarthritis-uy5dcn7w.pdf

Mesenchymal Stem Cell-based Cytotherapy for Osteoarthritis Management: State of the Art

Focal articular cartilage lesions of the knee are a challenging disease entity due to the poor regenerative properties of hyaline cartilage that often lead to degenerative joint disease. Surgery is indicated to alleviate symptoms, restore function, and return to desired activities when conservative treatment fails. Providers must consider defect size and severity, compliance with the postoperative rehabilitation protocol including weight-bearing restrictions, and patient expectations in their clinical decision-making. Smaller defects may be treated with arthroscopic chondroplasty, bone marrow stimulation, and osteochondral autologous transfer. Alternative surgical options for larger defects include osteochondral restoration using fresh vs. cryopreserved allografts, autologous chondrocyte implantation, and particulated juvenile allograft cartilage. This article will review available treatment options and provide an evidence-based treatment algorithm to guide the orthopaedic clinician's clinical decision-making.

Management of Articular Cartilage Defects in the Knee: An Evidence-Based Algorithm

Adipose tissue is widely recognized as an abundant and accessible human tissue that serves as a source of cells and extracellular matrix scaffolds for regenerative surgical applications. Increasingly, orthopedic surgeons are turning to adipose tissue as a resource in their treatment of osteoarthritis and related conditions. In the U.S., the regulatory landscape governing the orthopedic surgical utilization of autologous and allogeneic adipose tissue remains complex. This manuscript reviews the Food and Drug Administration's nomenclature and guidance regarding adipose tissue products. Additionally, it surveys recent pre-clinical and clinical trial literature relating to the application of adipose-derived cells and tissues in the treatment of osteoarthritis. 

https://doi.org/10.1016/j.bonr.2022.101601

Non-homologous use of adipose-derived cell and tissue therapies: Osteoarthritis as a case study

Introduction Osteoarthritis causes a progressive deterioration to the protective cartilage between the joints leading to chronic pain and disability. This review focuses on the intrinsic potential of MSCs to stabilize and repair the cartilage tissue of the knee joint in knee osteoarthritis (KOA) patients. Methods An online search through the PubMed database was conducted, limiting the search to the English language and human clinical trials within the past 5 years. Twenty-one clinical trials passed the inclusion criteria. Combined, those trials involved the participation of 589 patients where the progress of the treatments was monitored between a 4-month to 7-years period. The cartilage volume and defects were observed through an MRI to provide an objective assessment. While the pain and knee function were monitored using KOOS, VAS, and WOMAC scoring scales providing a subjective assessment. Results MRI scans obtained from clinical trials demonstrate a slowed progression of cartilage degeneration and early signs of cartilage regeneration in KOA patients at the 12-month follow-up period. No major adverse effects were observed post-intervention. The overall KOOS, WOMAC, and VAS scores in patients receiving MSC treatment were reduced, suggesting subjective improvements in knee function and pain reduction when compared to patients in the placebo group. Conclusion The use of MSC therapy is a valid form of treatment for KOA as it targets the disease itself rather than the symptoms. We found MSC therapy in KOA patients to be safe, effective, and feasible in its execution.

/pdf/clinical-applicability-of-adult-human-mesenchymal-stem-cell-2f17y9egc6.pdf

Clinical Applicability of Adult Human Mesenchymal Stem Cell Therapy in the Treatment of Knee Osteoarthritis.

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Clinical Applicability of Adult Human Mesenchymal Stem Cell Therapy in the Treatment of Knee Osteoarthritis.